Project Summary/Abstract Hematopoietic stem cells (HSCs) and skeletal stem cells (SSCs) persist throughout adult life to maintain homeostasis in the blood and skeletal systems, respectively. Both HSCs and SSCs usually localize adjacent to blood vessels in the bone marrow. Endothelial cells promote the maintenance and function of HSCs and SSCs, possibly by secreting growth factors. However, all known HSC niche factors in the bone marrow are more abundantly expressed by Leptin Receptor positive (LepR+) perivascular stromal cells than by endothelial cells. No HSC growth factors have yet been found to be produced primarily by bone marrow endothelial cells. It is also unclear whether endothelial cells secrete growth factors that regulate SSC maintenance. Given that endothelial cells are a prominent cellular component of bone marrow blood vessels, we hypothesize that they are likely to secrete factors that regulate the function of HSCs and/or SSCs in the bone marrow. In this proposal, I will characterize a new growth factor which is primarily synthesized by endothelial cells in the bone marrow. My preliminary data suggested that Crispld1 deletion depletes HSCs/MPPs as well as trabecular bone in the bone marrow. These data indicate that Crispld1 may regulate the function of both HSCs and SSCs. Characterization of this factor has the potential to provide new insights into the regulation of stem cell function as well as new strategies for regenerative medicine.